Study of Trace Elements and Role of Zinc Supplementation in Children with Idiopathic Intractable Epilepsy

Abstract

Background Trace elements have physiological effects on neuronal excitability that may play a role in the etiology of intractable epilepsy. The aim was to evaluate the possible associations between some trace elements and idiopathic intractable epilepsy in children, and also the role of zinc supplementation in reduction of seizures in such patients.

Materials and Methods Our study was designed as a case-control study with 80 idiopathic epileptic patients between the ages of 10 months and 14 years enrolled in the study, 45 intractable to treatment (Group I) and 35 controlled by treatment (Group II). Serum levels of selenium, zinc, and copper were measured with atomic absorption spectrophotometer. Group I patients were subdivided according to zinc supplementation into two subgroups. Group IA included 31 epileptic patients with refractory response and oral zinc supplementation for 4 months and Group IB included 14 epileptic patients with refractory response and without zinc supplementation with continuous follow-up of patients for further 6 months for evaluation of seizure recurrence.

Results We found that Group I patients had significantly lower levels of serum Se and Zn compared with those of Group II patients (p < 0.05). Serum copper levels were not significantly lower in Group I than Group II. Zinc supplementation resulted in a significant reduction of seizure in Group I A compared with Group IB. Recurrence of seizure activity after discontinuation of zinc supplementation was significant in Group IA (p < 0.01).

Conclusions We found significantly lower serum levels of zinc and selenium in patients with intractable epilepsy as compared to the controlled epilepsy group. Zinc supplementation had a significant role in reduction of seizures in such patients.

Keywords

trace elements - intractable epilepsy - controlled epilepsy - zinc supplementation

• References

• 1 Camfield PR, Camfield CS. Pediatric epilepsy: an overview. In: Swaiman KF, Ashwal S, Ferriero DM, eds. Pediatric Neurology: Principles & Practice. Philadelphia, PA: Mosby; 2006: 981-991
• 2 Mikati MA. Seizures in childhood. In: Kliegman RM, Stanton BF, Schor NF, Geme JWS, Behrman R, eds. Nelson Textbook of Pediatrics. 19th ed. Philadelphia, PA: Saunders Elsevier; 2011: 2013-2033
• 3 Kwan P, Brodie MJ. Early identification of refractory epilepsy. N Engl J Med 2000; 342 (5) 314-319
• 4 Hao XT, Wong ISM, Kwan P. Interrater reliability of the international consensus definition of drug-resistant epilepsy: a pilot study. Epilepsy Behav 2011; 22 (2) 388-390
• 5 Ulvi H, Yiðiter R, Yoldaþ T, Dolu Y, Var A, Müngen B. Magnesium, zinc and copper contents in hair and their serum concentrations in patients with epilepsy. East J Med 2002; 7 (2) 31-35
• 6 Mizielinska SM. Ion channels in epilepsy. Biochem Soc Trans 2007; 35 (Pt 5): 1077-1079
• 7 Hamed SA, Abdellah MM, El-Melegy N. Blood levels of trace elements, electrolytes, and oxidative stress/antioxidant systems in epileptic patients. J Pharmacol Sci 2004; 96 (4) 465-473
• 8 Hayashi M. Oxidative stress in developmental brain disorders. Neuropathology 2009; 29 (1) 1-8
• 9 Horning MS, Blakemore LJ, Trombley PQ. Endogenous mechanisms of neuroprotection: role of zinc, copper, and carnosine. Brain Res 2000; 852 (1) 56-61
• 10 Institute of Medicine. Institute of Medicine Dietary Reference Intakes: The Essential Guide to Nutrient Requirements. Washington, DC: National Academies Press; 2006
• 11 Ananth NR. Trace elements estimation: methods and clinical context. Online J Health Appl Sci 2005; 4: 2-3
• 12 Ashrafi MR, Shabanian R, Abbaskhanian A , et al. Selenium and intractable epilepsy: is there any correlation?. Pediatr Neurol 2007; 36 (1) 25-29
• 13 Salwen MJ. Vitamins and trace elements. In: Pherson RA, Pincus MR, eds. Henry's Clinical Diagnosis and Management by Laboratory Methods. 21st ed. Philadelphia, PA: Saunders; 2007: 379-389
• 14 Farzin L, Moassesi ME, Sajadi F, Amiri M, Shams H. Serum levels of antioxidants (Zn, Cu, Se) in healthy volunteers living in Tehran. Biol Trace Elem Res 2009; 129 (1–3) 36-45
• 15 McEwan MJ, Espie CA, Metcalfe J. A systematic review of the contribution of qualitative research to the study of quality of life in children and adolescents with epilepsy. Seizure 2004; 13 (1) 3-14
• 16 Yüksel A, Cengiz M, Seven M, Ulutin T. Erythrocyte glutathione, glutathione peroxidase, superoxide dismutase and serum lipid peroxidation in epileptic children with valproate and carbamazepine monotherapy. J Basic Clin Physiol Pharmacol 2000; 11 (1) 73-81
• 17 Ashrafi MR, Shams S, Nouri M , et al. A probable causative factor for an old problem: selenium and glutathione peroxidase appear to play important roles in epilepsy pathogenesis. Epilepsia 2007; 48 (9) 1750-1755
• 18 Yüksel A, Cengiz M, Seven M, Ulutin T. Changes in the antioxidant system in epileptic children receiving antiepileptic drugs: two-year prospective studies. J Child Neurol 2001; 16 (8) 603-606
• 19 Savaskan NE, Bräuer AU, Kühbacher M , et al. Selenium deficiency increases susceptibility to glutamate-induced excitotoxicity. FASEB J 2003; 17 (1) 112-114
• 20 Ramaekers VT, Calomme M, Vanden Berghe D, Makropoulos W. Selenium deficiency triggering intractable seizures. Neuropediatrics 1994; 25 (4) 217-223
• 21 Seven M, Basaran SY, Cengiz M, Unal S, Yuksel A. Deficiency of selenium and zinc as a causative factor for idiopathic intractable epilepsy. Epilepsy Res 2013; 104 (1–2) 35-39
• 22 Wojciak RW, Mojs E, Stanislawska-Kubiak M, Samborski W. The serum zinc, copper, iron, and chromium concentrations in epileptic children. Epilepsy Res 2013; 104 (1–2) 40-44
• 23 Prasad DKV, Shaheen U, Satyanarayana U, Surya Prabha T, Jyothy A, Munshi A. Association of serum trace elements and minerals with genetic generalized epilepsy and idiopathic intractable epilepsy. Neurochem Res 2014; 39 (12) 2370-2376
• 24 Mathie A, Sutton GL, Clarke CE, Veale EL. Zinc and copper: pharmacological probes and endogenous modulators of neuronal excitability. Pharmacol Ther 2006; 111 (3) 567-583
• 25 Schrauzer GN. The nutritional significance, metabolism and toxicology of selenomethionine. Adv Food Nutr Res 2003; 47: 73-112
• 26 Liochev SI, Fridovich I. Copper- and zinc-containing superoxide dismutase can act as a superoxide reductase and a superoxide oxidase. J Biol Chem 2000; 275 (49) 38482-38485
• 27 Saad K, Hammad E, Asmaa Hassan A, Badry R. Trace element, oxidant, and antioxidant enzyme values in blood of children with refractory epilepsy. Int J Neurosci 2014; 124 (3) 181-186
• 28 Prasad R, Singh A, Das BK. Cerebrospinal fluid and serum zinc, copper, magnesium and calcium levels in children with idiopathic seizures. J Clin Diagn Res 2009; 3: 1841-1846
• 29 Verrotti A, Basciani F, Trotta D, Pomilio MP, Morgese G, Chiarelli F. Serum copper, zinc, selenium, glutathione peroxidase and superoxide dismutase levels in epileptic children before and after 1 year of sodium valproate and carbamazepine therapy. Epilepsy Res 2002; 48 (1–2) 71-75
• 30 Chen D, Lu Y, Yu W , et al. Clinical value of decreased superoxide dismutase 1 in patients with epilepsy. Seizure 2012; 21 (7) 508-511
• 31 Armutcu F, Ozerol E, Gurel A , et al. Effect of long-term therapy with sodium valproate on nail and serum trace element status in epileptic children. Biol Trace Elem Res 2004; 102 (1–3) 1-10
• 32 Kheradmand Z, Yarali B, Zare A, Pourpak Z, Shams S, Ashrafi MR. Comparison of serum zinc and copper levels in children and adolescents with intractable and controlled epilepsy. Iran J Child Neurol 2014; 8 (3) 49-54
• 33 Thiel RJ, Fowkes SW. Down syndrome and epilepsy: a nutritional connection?. Med Hypotheses 2004; 62 (1) 35-44
• 34 Dudek FE. Zinc and epileptogenesis. Epilepsy Curr 2001; 1 (2) 66-70
• 35 Takeda A, Hirate M, Tamano H, Nisibaba D, Oku N. Susceptibility to kainate-induced seizures under dietary zinc deficiency. J Neurochem 2003; 85 (6) 1575-1580
• 36 Zaccara G, Perucca E. Interactions between antiepileptic drugs, and between antiepileptic drugs and other drugs. Epileptic Disord 2014; 16 (4) 409-431
• 37 Takeda A. Zinc homeostasis and functions of zinc in the brain. Biometals 2001; 14 (3–4) 343-351
• 38 Armutcu F, Ozerol E, Gurel A , et al. Effect of long-term therapy with sodium valproate on nail and serum trace element status in epileptic children. Biol Trace Elem Res 2004; 102 (1–3) 1-10
• 39 Karimooy HN, Hajzadeh MA, Haidari R, Hosseini M. Serum zinc and copper levels in untreated epileptic patients. Pharmacologyonline 2008; 2: 471-479